The long-range objective of the proposal is to develop plasma membrane modifiers and inhibitors affecting the viability and social behavior of the cancer cells and hopefully increasing their immunogenicity and permeability with respect to anti-cancer drugs. The following two approaches will be attempted: (1) Analogs of certain amino sugars (D-glucosamine, D-galactosamine, D-mannosamine, and sialic acid) and of L-fucose and 6-doexy-D-mannose) will be synthesized and tested in various systems, among which those designed to determine changes in cell membrane function are given prominence. (2) Potential inhibitors of cell surface glycosyltransferases, viz. some nucleotide sugar analogs, will be prepared. Biological and biochemical testing of the compounds will be carried out in hexokinase and on P288 murine leukemia cells both in vitro and in vivo. In vitro tests are designed to evaluate the effect of the compounds on cell growth and on the synthesis of glycoprotein and protein membrane components. In vivo tests are primarily designed to detect changes in membrane function or antigenicity. BIBLIOGRAPHIC REFERENCES: Yang, L., Harris, C.M., Metzler, D.E., Korytnyk, W., Lachmann, B., and Potti, P.G.G. Properties of 4-Ethenyl and 4-Ethynyl Analogs of Pyridoxal Phosphate and Their Reactions with the APO Form of Aspartate Aminotransferase. J. Biol. Chem. 250: 2947, 1975. Paul, B., Bernacki, R.J., and Korytnyk, W., Synthesis and Biological Activity of Some 1-N-Substituted 2-Acetamido-2-deoxy-beta-D-glucopyranosylamine Derivatives and Their Analogs. Abstracts, 170th Meeting Am. Chem. Soc., Chicago, August 1975, MEDI 144.